title: The effects of P2X receptor agonists on renal sodium and water excretion in anaesthetized rats.
abstract: OBJECTIVE
  To investigate in vivo effects of P2X receptor activation on sodium and water excretion in urine.
  
  
  METHODS
  The clearance experiments were carried out in anaesthetized rats during intravenous infusion (2 μmol kg(-1) + 20 nmol (kg min)(-1) , v = 40 μL min(-1)) of P2X receptors agonists: α,β-methylene ATP (α,β-meATP) and β,γ-methylene ATP (β,γ-meATP). Cortical blood flow (CBF) was estimated by laser Doppler flux during intrarenal artery infusion of β,γ-meATP (20 nmol (kg min)(-1) , v = 2 μL min(-1)). Influence of α,β-meATP and β,γ-meATP on the activity of Na-K-ATPase was investigated in isolated proximal tubules.
  
  
  RESULTS
  Intravenous infusion of β,γ-meATP resulted in a marked, progressively increasing diuresis and this effect was accompanied by a progressive increase in the sodium excretion rate. The glomerular filtration rate was unaffected. The effects of β,γ-meATP were abolished by P2 receptor antagonist PPADS (70 nmol (kg min)(-1)). CBF increased by 16 ± 2% during renal artery infusion of β,γ-meATP. Furthermore, α,β-meATP and β,γ-meATP increased 1.5-fold lithium clearance (C(Li)). Sodium excretion, expressed as a fraction of the distal delivery (C(Na) C(Li) (-1)), increased 1.5-fold during infusion of α,β-meATP or β,γ-meATP. Both agonists at 10(-6) (M) produced a statistical significant decrement in the ouabain-sensitive ATPase activity about 16-20% and these effects were blocked in the presence of PPADS.
  
  
  CONCLUSIONS
  Activation of P2X receptors increased renal sodium and water excretion. Mechanistically, P2X agonists increased renal perfusion and inhibited sodium reabsorption via an Na-K-ATPase-dependent mechanism.
authors.affiliation: Department of Therapy Monitoring and Pharmacogenetics, Medical University of Gdansk, Poland. majank@gumed.edu.pl
authors.forename: M
authors.initials: M
authors.lastname: Jankowski
authors.forename: E
authors.initials: E
authors.lastname: Szamocka
authors.forename: R
authors.initials: R
authors.lastname: Kowalski
authors.forename: S
authors.initials: S
authors.lastname: Angielski
authors.forename: M
authors.initials: M
authors.lastname: Szczepańska-Konkel
mesh_terms: D000818:Animals; D005919:Glomerular Filtration Rate; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D058911:Purinergic P2X Receptor Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D058469:Receptors, Purinergic P2X / Q000378:metabolism*; D012039:Regional Blood Flow; D012077:Renal Artery / Q000378:metabolism; D012964:Sodium / Q000652:urine*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014867:Water / Q000378:metabolism*
chemical_list: D058911:Purinergic P2X Receptor Agonists; D058469:Receptors, Purinergic P2X; D014867:Water; C011265:guanosine 5'-(beta,gamma-methylene)triphosphate; D006160:Guanosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase